Abstract
It is now recognized that extracellular Ca 2+ can regulate the functional activity of particular types of cells in the body. Many of these cells are involved in maintaining body Ca 2+ homeostasis and are present in certain endocrine glands and in bone, kidney, and the intestine. Notable among these cells are parathyroid cells which secrete parathyroid hormone (PTH). PTH acts on bone and kidney to increase the level of Ca 2+ in blood and extracellular fluids and plays a major role in maintaining body homeostasis. Parafollicular cells in the thyroid, or C-cells, secrete the hormone calcitonin which acts to decrease plasma levels of Ca 2+ . The secretion of both PTH and calcitonin is regulated by changes in the concentration of extracellular Ca 2+ : increased levels of extracellular Ca 2+ inhibit PTH secretion and stimulate calcitonin secretion. The effects of extracellular Ca 2+ are mediated by a cell surface Ca 2+ receptor protein. The parathyroid cell Ca 2+ receptor has been cloned and is a member of the G protein-coupled receptor superfamily. In parathyroid cells, the Ca 2+ receptor is coupled to phospholipase C and its activation by extracellular Ca 2+ results in the inositol 1,4,5-trisphosphate-induced release of intracellular Ca 2+ , which is associated with an inhibition of PTH secretion. Other cells, such as osteoclasts in bone are also responsive to changes in the concentration of extracellular Ca 2+ , although the structure of the putative Ca 2+ receptor on these cells is still unknown. The recognition of a wide array of cells scattered throughout the body that can detect and respond to changes in the concentration of extracellular Ca 2+ provides evidence for a signaling role of extracellular Ca 2+ that is functionally akin to molecular ligands such as hormones and neurotransmitters. The cell surface Ca 2+ receptors expressed on these cells provide novel molecular targets for new drugs to treat a variety of disease states.
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